Direct Regulation of Myocardial Triglyceride Metabolism by the Cardiomyocyte Circadian Clock

摘要: Maintenance of circadian alignment between an organism and its environment is essential to ensure metabolic homeostasis. Synchrony achieved by cell autonomous clocks. Despite a growing appreciation the integral relation clocks metabolism, little known regarding direct influence peripheral clock on cellular responses fatty acids. To address this important issue, we utilized genetic model disrupted function specifically in cardiomyocytes vivo (termed cardiomyocyte mutant (CCM)). CCM mice exhibited altered myocardial response chronic high fat feeding at levels transcriptome lipidome as well fluxes, providing evidence that regulates triglyceride metabolism. Time-of-day-dependent oscillations levels, net synthesis, lipolysis were markedly attenuated hearts. Analysis key proteins influencing turnover suggest inactivates hormone-sensitive lipase during active/awake phase both transcriptional post-translational (via AMP-activated protein kinase) levels. Consistent with increased synthesis end phase, time resulted marked cardiac steatosis. These data provide for regulation reveal potential mechanistic explanation accelerated pathologies after prevalent misalignment Western society.